2024 World Conference on Lung Cancer (WCLC) - Posters-P1.06B.14 Optimal Cut-Off with NGS for Metamplification Andclinical Relevance to MET Inhibitor in Non-Small-Cell Lung Cancer

P1.06B.14 Optimal Cut-Off with NGS for Metamplification Andclinical Relevance to MET Inhibitor in Non-Small-Cell Lung Cancer

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The study aimed to determine the optimal cut-off value for MET amplification using next-generation sequencing (NGS) in non-small cell lung cancer (NSCLC) patients and its clinical relevance to MET inhibitor treatment. Traditionally, MET amplification is assessed using fluorescence in situ hybridization (FISH), but NGS is now widely used due to its ability to detect various genomic alterations. However, there is no unified standard cut-off for MET amplification in NGS assays.<br /><br />Researchers conducted a multi-site study to define an appropriate cut-off value. The study utilized a training cohort of 21 patients to compare MET gene copy numbers using five different NGS panels against the FISH standard. Receiver operating characteristic (ROC) analysis identified a MET gene copy number (GCN) cut-off of 6.55 in NGS, which provided an accuracy of 85.7% and an area under the curve of 0.9.<br /><br />A validation cohort of 29 patients was then used to confirm the cut-off's predictive value. In this cohort, the accuracy rate was 79.3%, and patients with a MET GCN of 6.55 had significantly longer progression-free survival compared to those with a lower GCN. The NGS-based MET amplification with a cut-off of 6.55 was established as an independent factor linked to significant progression-free survival benefits in both univariable and multivariable analyses.<br /><br />The study concludes that a MET GCN cut-off of 6.55 is optimal for NGS tissue analysis in NSCLC, indicating that MET amplification at this level is beneficial for survival when patients undergo targeted therapy. Future research is necessary to further validate these findings. The study was a collaboration among various institutes and acknowledges contributions from several researchers.

Asset Subtitle

Si-Yang Liu

Meta Tag

Speaker Si-Yang Liu

Topic Pathology & Biomarkers

Keywords

MET amplification

next-generation sequencing

non-small cell lung cancer

NSCLC

MET inhibitor treatment

fluorescence in situ hybridization

FISH

gene copy number

progression-free survival

targeted therapy